Estrogen-responsive tissues contain significant levels of cytoplasmic receptors which interact with the estrogen as the initial step in the hormone's action. The proposed studies are focused on an investigation of the effects of a number of different natural and synthetic compounds on the levels, functionality and intracellular distribution of estrogen receptors in the anterior pituitary and hypothalamus. Specific studies will include analysis of estrogenic regulation of dynamics (including synthesis, activiation, re-cycling and reutilization), assessment of the nature and steroidal specificity of the induction of the receptor depletion-replenishment phenomenon, further characterization of thyroid hormone-estrogen receptor interactions, exploration of the general applicability of kinetic measurements of steriod-receptor interactions, and investigation of the molecular relationships between luteinizing-hormone releasing hormone (LHRH) and estrogen receptors. The results of this work, and of other experiments utilizing the sterile neonatally-androgenized rat as a model, should provide a better understanding of the factors contributing to the profound influence of estrogens on gonadotropin secretion and ovulation.